Exchange Broadening Underlies the Enhancement of IDE-Dependent Degradation of Insulin by Anionic Membranes.

ABSTRACT: Insulin-degrading enzyme (IDE) is an evolutionarily conserved ubiquitous zinc metalloprotease implicated in the efficient degradation of insulin monomer. However, IDE also degrades monomers of amyloidogenic peptides associated with disease, complicating the development of IDE inhibitors. In this work, we investigated the effects of the lipid composition of membranes on the IDE-dependent degradation of insulin. Kinetic analysis based on chromatography and insulin's helical circular dichroic signal showed that the presence of anionic lipids in membranes enhances IDE's activity toward insulin. Using NMR spectroscopy, we discovered that exchange broadening underlies the enhancement of IDE's activity. These findings, together with the adverse effects of anionic membranes in the self-assembly of

SUBMITTER: Zheng Q 

PROVIDER: S-EPMC9301717 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature